| First Author | Ghosh C | Year | 2024 |
| Journal | Dev Cell | PubMed ID | 38452758 |
| Mgi Jnum | J:346747 | Mgi Id | MGI:7618049 |
| Doi | 10.1016/j.devcel.2024.02.005 | Citation | Ghosh C, et al. (2024) Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls cell sensitivity to interferon. Dev Cell |
| abstractText | The interferon signaling pathway is critical for host defense by serving diverse functions in both innate and adaptive immune responses. Here, we show that type I gamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIgammai5), an enzyme that synthesizes phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)), controls the sensitivity to interferon in both human and mouse cells. PIPKIgammai5 directly binds to the interferon-gamma (IFN-gamma) downstream effector signal transducer and activator of transcription 1 (STAT1), which suppresses the STAT1 dimerization, IFN-gamma-induced STAT1 nuclear translocation, and transcription of IFN-gamma-responsive genes. Depletion of PIPKIgammai5 significantly enhances IFN-gamma signaling and strengthens an antiviral response. In addition, PIPKIgammai5-synthesized PI4,5P(2) can bind to STAT1 and promote the PIPKIgammai5-STAT1 interaction. Similar to its interaction with STAT1, PIPKIgammai5 is capable of interacting with other members of the STAT family, including STAT2 and STAT3, thereby suppressing the expression of genes mediated by these transcription factors. These findings identify the function of PIPKIgammai5 in immune regulation. |
